Click Chemistry: developing new tools & reactions for practical applications

This thesis primarily concerns the development of new tools and reactions through the activation of chemical moieties to generate either function, as protein labels or the synthetically valuable sulfonyl azides, or unusual chemical reactivity. Chapter 1 contains a brief introduction to the concept of Click Chemistry, with an overview of the nature of Click Chemistry reactions and their corresponding applications. Chapter 2 focusses on the use of diazirines, high energy but remarkably stable functionality as tools to probe protein structure. A protein footprinting technique has been developed employing aromatic based diazirine photoactive labels to decorate the protein surface. Following analysis by mass spectrometry, information could be inferred regarding the binding site of an Ub-IsoT ZnF protein complex. In addition, a range of diazirine probes of varying steric and electronic demands have been synthesised and their labelling properties characterised. The recently developed SuFEx activation has been applied in Chapter 3, with the development of a protocol for formation of sulfonyl azides from the robust sulfonyl fluorides. The methodology was extended to an in situ diazo transfer reaction, which circumvents the requirement to handle the potentially unstable diazo transfer reagent. Additionally, it was the pursuit of a novel mode of activation for the azide-alkyne cycloaddition, which generated a serendipitous result that led to the results in Chapter 4. Radical cation activation led to a selection of reactive intermediates that engaged in unusual chemistry